tbuckley/cabot-search huggingface dataset:
Clinical Features and Risk Factors Associated With Multisystem Inflammatory Syndrome in Children With Cancer and COVID-19
Authors: Samantha D. Martin, Elizabeth S. Davis, Chen Dai, Lauren H. Boal, Brook Araya, Julienne Brackett, David Dickens, Alissa Kahn, Isaac Martinez, Archana Sharma, Carla Schwalm, Paibel Aguayo-Hiraldo, Smita Bhatia, Jennifer M. Levine, Emily E. Johnston, Julie A. Wolfson, Catherine Aftandilian, Anurag K. Agrawal, Guillermo De Angulo, Paula Aristizabal, Kayleen Bailey, Jenna K. Bardwell, David L. Becton, Christina J. Bemrich-Stolz, Lauren H. Boal, Catherine W.H. Boston, Scott M. Bradﬁeld, Emi H. Caywood, Shannon M. Cohn, Susan I. Colace, Scott L. Coven, Stuart L. Cramer, Branko Cuglievan, Jamie L. Dargart, Doured Daghistani, Aditi Dhir, David S. Dickens, Anca Dumitriu, Don E. Eslin, Jose M. Esquilin, Shari L. Feinberg, Asmaa Ferdjallah, Karen S. Fernandez, Jason Fixler, Jessica M. Foley, Bradley H. Gampel, Chana L. Glasser, Jessica F. Goodman, Moran Gotesman, L. Kate Gowans, Ajay Gupta, Josephine H. HaDuong, Steven L. Halpern, Harneet K. Hara, Lisa R. Hartman, Katye L. Herring, Caroline S. Hesko, Paibel Aguayo-Hiraldo, Alice K. Hoeft, Caroline Y. Hu, Jeffrey S. Huo, Alan K. Ikeda, Michael S. Isakoff, Akshat Jain, Alissa R. Kahn, Prachi D. Kothari, Jennifer A. Krajewski, David E. Kram, Julie I. Krystal, Wade T. Kyono, Mary A. Langevin, Brandon Hayes-Lattin, Jason Law, Jennifer M. Levine, Adonis N. Lorenzana, Craig D. Lotterman, Fataneh Majlessipour, Preethi R. Marri, Gita V. Massey, Philip M. Monteleone, Amy M. Moskop, Catriona Mowbray, Pournima D. Navalkele, Janice F. Olson, Leanne Ostrodka, Chibuzo C. O’suoji, Pratik A. Patel, Anna Pawlowska, Anna Sechser Perl, Ashley E. Pinchinat, Pinki K. Prasad, Arun A. Rangaswami, Chittalsinh M. Raulji, Juan F. Rico, Aniket Saha, Emad K. Salman, Nadine P. SantaCruz, Susmita N. Sarangi, Carla M. Schwalm, Archana Sharma, Peter H. Shaw, David C. Simon, William B. Slayton, Amy A. Smith, Andrew B. Smitherman, Caryn E. Sorge, Jessica M. Sun, Heather J. Symons, Adit Tal, Stefanie M. Thomas, Hung C. Tran, Jacob A. Troutman, Lucie M. Turcotte, Jessica M. Valdez, Carly R. Varela, Nicholas S. Whipple, Jennifer J. Wilkes, Wendy Woods-Swafford, Yung S. Yim, Yaoping Zhang
Journal: JAMA Oncology (2023)

Little is known about the risk of post-COVID-19 multisystem inflammatory syndrome in children (MIS-C) in the setting of childhood cancer.
AR-A014418 regulates intronic polyadenylation and transcription of PD-L1 through inhibiting CDK12 and CDK13 in tumor cells
Authors: Ganggang Zhang, Bin Lan, Xin Zhang, Mengyao Lin, Yi Liu, Junsong Chen, Fang Guo
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Immune checkpoint molecules, especially programmed death 1 (PD-1) and its ligand, programmed death ligand 1 (PD-L1), protect tumor cells from T cell-mediated killing. Immune checkpoint inhibitors, designed to restore the antitumor immunosurveillance, have exhibited significant clinical benefits for patients with certain cancer types. Nevertheless, the relatively low response rate and acquisition of resistance greatly limit their clinical applications. A deeper understanding of the regulatory mechanisms of PD-L1 protein expression and activity will help to develop more effective therapeutic strategies. Methods The effects of AR-A014418 and THZ531 on PD-L1 expression were detected by western blot, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and flow cytometry. In vitro kinase assays with recombinant proteins were performed to confirm that AR-A014418 functioned as a CDK12 and CDK13 dual inhibitor. The roles of CDK12 and CDK13 in intronic polyadenylation (IPA) and transcription of PD-L1 were determined via RNA interference or protein overexpression. T-cell cytotoxicity assays were used to validate the activation of antitumor immunity by AR-A014418 and THZ531. Results AR-A014418 inhibits CDK12 to enhance the IPA, and inhibits CDK13 to repress the transcription of PD-L1. IPA generates a secreted PD-L1 isoform (PD-L1-v4). The extent of IPA was not enough to reduce full-length PD-L1 expression obviously. Only the superposition of enhancing IPA and repressing transcription (dual inhibition of CDK12 and CDK13) dramatically suppresses full-length PD-L1 induction by interferon-γ. AR-A014418 and THZ531 could potentiate T-cell cytotoxicity against tumor cells. Conclusions Our work identifies a new regulatory pathway for PD-L1 expression and discovers CDK12 and CDK13 as promising drug targets for immune modulation and combined therapeutic strategies.
SELENOP modifies sporadic colorectal carcinogenesis and WNT signaling activity through LRP5/6 interactions
Authors: Jennifer M. Pilat, Rachel E. Brown, Zhengyi Chen, Nathaniel J. Berle, Adrian P. Othon, M. Kay Washington, Shruti A. Anant, Suguru Kurokawa, Victoria H. Ng, Joshua J. Thompson, Justin Jacobse, Jeremy A. Goettel, Ethan Lee, Yash A. Choksi, Ken S. Lau, Sarah P. Short, Christopher S. Williams
Journal: Journal of Clinical Investigation (2023)

Although selenium deficiency correlates with colorectal cancer (CRC) risk, the roles of the selenium-rich antioxidant selenoprotein P (SELENOP) in CRC remain unclear. In this study, we defined SELENOP's contributions to sporadic CRC. In human single-cell cRNA-Seq (scRNA-Seq) data sets, we discovered that SELENOP expression rose as normal colon stem cells transformed into adenomas that progressed into carcinomas. We next examined the effects of Selenop KO in a mouse adenoma model that involved conditional, intestinal epithelium-specific deletion of the tumor suppressor adenomatous polyposis coli (Apc) and found that Selenop KO decreased colon tumor incidence and size. We mechanistically interrogated SELENOP-driven phenotypes in tumor organoids as well as in CRC and noncancer cell lines. Selenop-KO tumor organoids demonstrated defects in organoid formation and decreases in WNT target gene expression, which could be reversed by SELENOP restoration. Moreover, SELENOP increased canonical WNT signaling activity in noncancer and CRC cell lines. In defining the mechanism of action of SELENOP, we mapped protein-protein interactions between SELENOP and the WNT coreceptors low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6). Last, we confirmed that SELENOP-LRP5/6 interactions contributed to the effects of SELENOP on WNT activity. Overall, our results position SELENOP as a modulator of the WNT signaling pathway in sporadic CRC.
Human metabolome variation along the upper intestinal tract
Authors: Jacob Folz, Rebecca Neal Culver, Juan Montes Morales, Jessica Grembi, George Triadafilopoulos, David A. Relman, Kerwyn Casey Huang, Dari Shalon, Oliver Fiehn
Journal: Nature Metabolism (2023)

Most processing of the human diet occurs in the small intestine. Metabolites in the small intestine originate from host secretions, plus the ingested exposome
Surface Engineering of Central Venous Catheters via Combination of Antibacterial Endothelium‐Mimicking Function and Fibrinolytic Activity for Combating Blood Stream Infection and Thrombosis
Authors: Kaijun Li, Jinyu Peng, Yuqi Liu, Fanjun Zhang, Dimeng Wu, Rifang Luo, Zongliang Du, Li Yang, Gongyan Liu, Yunbing Wang
Journal: Advanced Healthcare Materials (2023)

Abstract Long‐term blood‐contacting devices (e.g., central venous catheters, CVCs) still face the highest incidence of blood stream infection and thrombosis in clinical application. To effectively address these complications, this work reports a dual‐functional surface engineering strategy for CVCs by organic integration of endothelium‐mimicking and fibrinolytic functions. In this proposal, a lysine (Lys)/Cu 2+ ‐incorporated zwitterionic polymer coating (defined as PDA/Lys/Cu‐SB) is designed and robustly fabricated onto commercial CVCs using a facile two‐step process. Initially, adhesive ene ‐functionalized dopamine is covalently reacted with Lys and simultaneously coordinated with bactericidal Cu 2+ ions, leading to the deposition of a PDA/Lys/Cu coating on CVCs through mussel foot protein inspired surface chemistry. Next, zwitterionic poly(sulfobetaine methacrylate) (pSB) brushes are grafted onto the PDA/Lys/Cu coating to endow lubricant and antifouling properties. In the final PDA/Lys/Cu‐SB coating, endothelium‐mimicking function is achieved by combining the catalytic generation of nitric oxide from the chelated Cu 2+ with antifouling pSB brushes, which led to significant prevention of thrombosis, and bacterial infection in vivo. Furthermore, the immobilized Lys with fibrinolytic activity show remarkably enhanced long‐term anti‐thrombogenic properties as evidenced in vivo by demonstrating the capability to lyse nascent clots. Therefore, this developed strategy provides a promising solution for long‐term blood‐contacting devices to combat thrombosis and infection.
Why is everyone talking about brain state?
Authors: Abigail S. Greene, Corey Horien, Daniel Barson, Dustin Scheinost, R. Todd Constable
Journal: Trends in Neurosciences (2023)

The rapid and coordinated propagation of neural activity across the brain provides the foundation for complex behavior and cognition. Technical advances across neuroscience subfields have advanced understanding of these dynamics, but points of convergence are often obscured by semantic differences, creating silos of subfield-specific findings. In this review we describe how a parsimonious conceptualization of brain state as the fundamental building block of whole-brain activity offers a common framework to relate findings across scales and species. We present examples of the diverse techniques commonly used to study brain states associated with physiology and higher-order cognitive processes, and discuss how integration across them will enable a more comprehensive and mechanistic characterization of the neural dynamics that are crucial to survival but are disrupted in disease.
Adhesive Wearable Sensors for Electroencephalography from Hairy Scalp
Authors: Anan Zhang, Abhijith Balamuraleekrishna Shyam, Alexandra McCalla Cunningham, Christopher Williams, Amanda Brissenden, Alex Bartley, Brian Amsden, Aristides Docoslis, Marianna Kontopoulou, Shideh Kabiri Ameri
Journal: Advanced Healthcare Materials (2023)

Abstract Electroencephalography has garnered interest for applications in mobile healthcare, human–machine interfaces, and Internet of Things. Conventional electroencephalography relies on wet and dry electrodes. Despite favorable interface impedance of wet electrodes and skin, the application of a large amount of gel at their interface with skin limits the electroencephalography spatial resolution, increases the risk of shorting between electrodes, and makes them unsuited for long‐term mobile recording. In contrast, dry electrodes are better suited for long‐term recordings but susceptible to motion artifacts. In addition, both wet and dry electrodes are non‐adhesive to the hairy scalp and mechanical support, or chemical adhesives are used to hold them in place. Herein, a conical microstructure array (CMSA) based sensor made of carbon nanotube‐polydimethylsiloxane composite is reported. The CMSA sensor is fabricated using the innovative, cost‐effective, and scalable method of viscosity‐controlled dip‐pull process. The sensor adheres to the hairy scalp by generating negative pressure in its conical microstructures when it is pressed against scalp. Aided by the application of a trace amount of gel, CMSA sensor establishes good electrical contact with the skin, enabling its applications in mobile electroencephalography over extended periods. Notably, the signal quality of CMSA sensors is comparable to that of medical‐grade wet gel electrodes.
Rapid cross-border emergence of NDM-5-producing Escherichia coli in the European Union/European Economic Area, 2012 to June 2022
Authors: Marius Linkevicius, Rémy A Bonnin, Erik Alm, Olov Svartström, Petra Apfalter, Rainer Hartl, Henrik Hasman, Louise Roer, Kati Räisänen, Laurent Dortet, Niels Pfennigwerth, Jörg B Hans, Ákos Tóth, Lilla Buzgó, Martin Cormican, Niall Delappe, Monica Monaco, Maria Giufrè, Antoni PA Hendrickx, Ørjan Samuelsen, Anna K Pöntinen, Manuela Caniça, Vera Manageiro, Jesús Oteo-Iglesias, María Pérez-Vázquez, Karin Westmo, Barbro Mäkitalo, Daniel Palm, Dominique L Monnet, Anke Kohlenberg
Journal: Eurosurveillance (2023)

Whole genome sequencing data of 874 Escherichia coli isolates carrying blaNDM-5 from 13 European Union/European Economic Area countries between 2012 and June 2022 showed the predominance of sequence types ST167, ST405, ST410, ST361 and ST648, and an increasing frequency of detection. Nearly a third (30.6%) of these isolates were associated with infections and more than half (58.2%) were predicted to be multidrug-resistant. Further spread of E. coli carrying blaNDM-5 would leave limited treatment options for serious E. coli infections.
Stigma Associated With Requesting Accommodations—the High Cost of Ableism in Medicine
Authors: Meaghan Roy-O’Reilly, Arghavan Salles
Journal: JAMA Network Open (2023)

Karina Pereira-Lima, PhD, MSc; Lisa M. Meeks, PhD, MA; Katherine E. T. Ross, BS, BA; Jasmine R. Marcelin, MD; Lydia Smeltz, BA; Elena Frank, PhD; Srijan Sen, MD, PhD
Antiviral polysaccharide and antiviral peptide delivering nanomaterials for prevention and treatment of SARS-CoV-2 caused COVID-19 and other viral diseases
Authors: Shahin Homaeigohar, Xuan Liu, Mady Elbahri
Journal: Journal of Controlled Release (2023)

Antiviral peptides and antiviral polysaccharides can play a major role in the prevention and treatment of emerging viral health problems. These antiviral compounds are biocompatible, environmentally friendly, non-toxic, and cost-effective, yet are poorly water soluble and vulnerable to enzymatic (protease) degradation within the aggressive intercellular microenvironment. Therefore, they should be properly protected and delivered to viruses and host cells by the well-designed nanocarriers that mimic viruses in terms of size, morphology, and smart function. This literature review is meant to introduce the latest advances (mainly within the past five years) in antiviral nano-assemblies comprising antiviral peptides or antiviral polysaccharides. To the best of our knowledge, there is no similar study in the literature that has solely and sufficiently investigated such antiviral nanomaterials partially or totally derived from nature. The rational classification of microorganism-, plant-, and animal-derived antiviral polysaccharide and antiviral peptide delivering nanomaterials and exploration of their relevant applications will clarify the promising capacity of these state-of-the-art materials for a number of technologies developed to inactivate viruses.
Monitoring persistent organic chemicals in Antarctica in support of global chemical policy: a horizon scan of priority actions and challenges
Authors: Susan Bengtson Nash, Pernilla Bohlin-Nizzetto, Cristobal Galban-Malagon, Simonetta Corsolini, Alessandra Cincinelli, Rainer Lohmann
Journal: The Lancet Planetary Health (2023)

Global production and emission of chemicals exceeds societal capacities for assessment and monitoring. This situation calls for improved chemical regulatory policy frameworks and increased support for expedited decision making within existing frameworks. The polar regions of the Earth represent unique sentinel areas for the study of global chemical behaviour, and data arising from these areas can strengthen existing policy frameworks. However, chemical pollution research and monitoring in the Antarctic is underdeveloped, with geopolitical complexities and the absence of legal recognition of international chemical policy serving to neutralise progress made in other global regions. This Personal View represents a horizon scan by the action group Input Pathways of Persistent Organic Pollutants to Antarctica, of the Scientific Committee for Antarctic Research. Four priority research and research facilitation gaps are outlined, with recommendations for Antarctica Treaty parties for strategic action against these priorities.
High level of complexity and global diversity of the 3q29 locus revealed by optical mapping and long-read sequencing
Authors: Feyza Yilmaz, Umamaheswaran Gurusamy, Trenell J. Mosley, Pille Hallast, Kwondo Kim, Yulia Mostovoy, Ryan H. Purcell, Tamim H. Shaikh, Michael E. Zwick, Pui-Yan Kwok, Charles Lee, Jennifer G. Mulle
Journal: Genome Medicine (2023)

High sequence identity between segmental duplications (SDs) can facilitate copy number variants (CNVs) via non-allelic homologous recombination (NAHR). These CNVs are one of the fundamental causes of genomic disorders such as the 3q29 deletion syndrome (del3q29S). There are 21 protein-coding genes lost or gained as a result of such recurrent 1.6-Mbp deletions or duplications, respectively, in the 3q29 locus. While NAHR plays a role in CNV occurrence, the factors that increase the risk of NAHR at this particular locus are not well understood.
High-throughput deep learning variant effect prediction with Sequence UNET
Authors: Alistair S Dunham, Pedro Beltrao, Mohammed AlQuraishi
Journal: Genome biology (2023)

Understanding coding mutations is important for many applications in biology and medicine but the vast mutation space makes comprehensive experimental characterisation impossible. Current predictors are often computationally intensive and difficult to scale, including recent deep learning models. We introduce Sequence UNET, a highly scalable deep learning architecture that classifies and predicts variant frequency from sequence alone using multi-scale representations from a fully convolutional compression/expansion architecture. It achieves comparable pathogenicity prediction to recent methods. We demonstrate scalability by analysing 8.3B variants in 904,134 proteins detected through large-scale proteomics. Sequence UNET runs on modest hardware with a simple Python package.
Analysis of Secondhand Smoke Exposure and Myopia Among Children Aged 6 to 8 Years in Hong Kong
Authors: Youjuan Zhang, Xiu Juan Zhang, Nan Yuan, Yuzhou Zhang, Yu Meng Wang, Fangyao Tang, Mandy P. Ng, Ian C. K. Wong, Patrick Ip, Ka Wai Kam, Alvin L. Young, Li Jia Chen, Clement C. Tham, Chi Pui Pang, Jason C. Yam
Journal: JAMA Network Open (2023)

Importance Secondhand smoke (SHS) exposure potentially threatens ocular health; however, its association with myopia is unknown. Objective To examine the association between SHS exposure and childhood myopia. Design, Setting, and Participants Cross-sectional data from the population-based Hong Kong Children Eye Study were used. Data were collected from March 5, 2015, to September 12, 2021, at The Chinese University of Hong Kong Eye Center. Participants included children aged 6 to 8 years. Secondhand smoke exposure was evaluated using a validated questionnaire. All participants underwent comprehensive ophthalmic and physical examinations. Exposure Secondhand smoke exposure. Main Outcomes and Measures Generalized estimating equations were constructed to examine the association of SHS exposure with spherical equivalent and axial length; logistic regression models, with myopia rate; and linear regression models, with myopia onset. Results A total of 12 630 children (mean [SD] age, 7.37 [0.88] years; 53.2% boys) were included in the analysis. Among the participants, 4092 (32.4%) had SHS exposure. After adjusting for age, sex, parental myopia, body mass index, near-work time, outdoor time, and family income, SHS exposure was associated with greater myopic refraction (β = −0.09 [95% CI, −0.14 to −0.03]) and longer axial length (β = 0.05 [95% CI, 0.02-0.08]). Children with SHS exposure were more likely to develop moderate (odds ratio [OR], 1.30 [95% CI, 1.06-1.59]) and high myopia (OR, 2.64 [95% CI, 1.48-4.69]). The association of SHS exposure with spherical equivalence and axial length was magnified in younger children. For each younger year of a child’s exposure to SHS, SHS exposure was associated with a 0.07-D decrease in spherical equivalence (β = 0.07 [95% CI, 0.01-0.13]) and a 0.05-mm increase in axial length (β = −0.05 [95% CI, −0.08 to −0.01]). Exposure to SHS was associated with an earlier mean (SD) age at onset of myopia (72.8 [0.9] vs 74.6 [0.6] months; P = .01). Every increase in SHS exposure in units of 10 cigarettes per day was associated with greater myopic refraction (β = −0.07 [95% CI, −0.11 to −0.02]), axial length (β = 0.04 [95% CI, 0.01-0.06]), and likelihood of developing moderate (OR, 1.23 [95% CI, 1.05-1.44]) and high myopia (OR, 1.75 [95% CI, 1.20-2.56]), and earlier myopia onset (β = −1.30 [95% CI, −2.32 to −0.27]). Conclusions and Relevance The findings of this cross-sectional study suggest that SHS exposure was associated with greater myopic refraction, longer axial length, greater likelihood of developing moderate and high myopia, and earlier myopia onset. The larger the quantity of SHS exposure and the younger the child, the more advanced myopia development and progression with which SHS exposure is associated.
Dynamic frailty risk assessment among older adults with multiple myeloma: A population-based cohort study
Authors: Hira Mian, Tanya M. Wildes, Ravi Vij, Matthew J. Pianko, Ajay Major, Mark A. Fiala
Journal: Blood Cancer Journal (2023)

Abstract Multiple myeloma (MM) is a cancer of older adults and those who are more frail are at high risk of poor outcomes. Current tools for identifying and categorizing frail patients are often static and measured only at the time of diagnosis. The concept of dynamic frailty (i.e. frailty changing over time) is largely unexplored in MM. In our study, adults with newly-diagnosed MM who received novel drugs between the years 2007–2014 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases. Using a previously published cumulative deficit approach, a frailty index score was calculated at diagnosis and each landmark interval (1-yr, 2-yr, 3-yr post diagnosis). The association of frailty with overall survival (OS) both at baseline and at each landmark interval as well as factors associated with worsening frailty status over time were evaluated. Overall, 4617 patients were included. At baseline, 39% of the patients were categorized as moderately frail or severely frail. Among those who had 3 years of follow-up, frailty categorization changed post diagnosis in 93% of the cohort (78% improved and 72% deteriorated at least at one time point during the follow up period). In a landmark analysis, the predictive ability of frailty at the time of diagnosis decreased over time for OS (Harrell’s C Statistic 0.65 at diagnosis, 0.63 at 1-yr, 0.62 at 2-yr, and 0.60 at 3-yr) and was inferior compared to current frailty status at each landmark interval. Our study is one of the first to demonstrate the dynamic nature of frailty among older adults with MM. Frailty may improve or deteriorate over time. Current frailty status is a better predictor of outcomes than frailty status at time of diagnosis, indicating the need for re-measurement in this high-risk patient population.